rs781844953

Positions:

chrX-48902398-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001032382.2(PQBP1):c.458G>A(p.Arg153Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000058 in 1,207,653 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

PQBP1
NM_001032382.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.18

Variant links:

Genes affected

PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]

PQBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17352402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PQBP1	NM_001032382.2 linkuse as main transcript	c.458G>A	p.Arg153Lys	missense_variant	5/7	ENST00000447146.7	NP_001027554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7 linkuse as main transcript	c.458G>A	p.Arg153Lys	missense_variant	5/7	1	NM_001032382.2	ENSP00000391759	P1	O60828-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33926

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000114

AC:

AN:

175215

Hom.:

AF XY:

0.0000165

AC XY:

AN XY:

60685

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000744

Gnomad SAS exome

AF:

0.0000554

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1095875

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361407

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000663

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33926

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 17, 2023

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 521346). This variant has not been reported in the literature in individuals affected with PQBP1-related conditions. This variant is present in population databases (rs781844953, gnomAD 0.008%), including at least one homozygous and/or hemizygous individual. This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 153 of the PQBP1 protein (p.Arg153Lys). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

T;T;T;T;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.68

T;.;.;.;.

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.46

N;N;N;N;.

MutationTaster

Benign

0.67

D;D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.28

N;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.29

T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.048

B;B;B;B;.

Vest4

0.12

MutPred

0.19

Gain of ubiquitination at R153 (P = 0.009);Gain of ubiquitination at R153 (P = 0.009);Gain of ubiquitination at R153 (P = 0.009);Gain of ubiquitination at R153 (P = 0.009);Gain of ubiquitination at R153 (P = 0.009);

MVP

0.69

MPC

1.1

ClinPred

0.11

GERP RS

5.2

Varity_R

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over